The major goal of this research is to define the molecular control mechanisms of the synthesis, secretion and activity of collagenase in human fibroblast cultures and, thus to understand its role in both normal and diseased tissues. Factors which may modulate the activity of this important enzyme will be investigated to assess their action at a cellular level. Cultures will be examined for collagenase activity, for immunoreactive protein and for a specific fibroblast-derived collagenase inhibitor. In addition, biosynthetic studies to assess rates of synthesis and degradation will be performed. These data may then allow us to understand the role of this enzyme both in normal collagen degradation and in the pathogenesis of such diseases as epidermolysis bullosa.